Pharmacologically active imidazole compounds with antiinflammatory activity are already known.
Thus, inter alia, compounds having 4,5-di(hetero)arylimidazole moieties have been examined more closely, and various pharmaceutical actions thereof have been described. Also known are compounds which are substituted in the 2-position. U.S. Pat. No. 4,585,771 discloses 4,5-diphenylimidazole derivatives which are substituted in the 2-position by a pyrrolyl, indolyl, imidazolyl or thiazolyl radical and which have antiinflammatory and antiallergic activity.
U.S. Pat. Nos. 4,528,298 and 4,402,960 describe 4,5-di(hetero)arylimidazole derivatives which are substituted in the 2-position via a thio, sulfinyl or sulfonyl group by a phenyl, pyridyl, N-oxypyridyl, pyrimidyl, thiazolyl or thienyl radical and which have antiinflammatory and antiallergic activity.
U.S. Pat. Nos. 4,461,770, 4,608,382 and 4,584,310 describe 4-(5-aryl)-5-(4-heteroaryl)imidazole derivatives which are substituted in the 2-position via a thio, sulfinyl or sulfonyl group by a substituted or unsubstituted aliphatic hydrocarbon and which, inter alia, have antiinflammatory action.
WO 00/17192 relates to 4-heteroaryl-5-phenylimidazole derivatives which are substituted in the 2-position by a phenylalkylthio group. These compounds act as antiinflammatories and inhibitors of cytokine release. WO 99/03837 and WO 93/14081 describe 2-substituted imidazoles which inhibit the synthesis of a number of inflammatory cytokines. The compounds described in WO 93/14081 have in the 2-position, attached via a sulfur atom, a phosphorus-containing substituent or an aryl or heteroaryl substituent. WO 91/10662 describes imidazole derivatives which inhibit the acyl-CoA: cholesterol 0-acyl transferase and binding of thromboxane TxA2. WO 95/00501 describes imidazole derivatives which can be used as cyclooxygenase inhibitors. The imidazole derivatives described in U.S. Pat. Nos. 4,440,776; 4,355,039 and 4,269,847 have antiinflammatory, antiallergic and immunostimulating action. DE 35 04 678 describes imidazole derivatives which can be used for treating atherosclerotic, thromboembolic and inflammatory diseases and diseases which are associated with lipid metabolism. GB 1 564 184 describes 2-polyfluoro-C1-C2-alkyl-substituted imidazole compounds having anti-inflammatory action. WO 96/03387 and WO 02/066485, too, describe substituted imidazole compounds having anti-inflammatory action.
J. Med. Chem. 1996, 39, 3927-37 describes compounds having 5-lipoxygenase- and cyclooxygenase-inhibiting action, 2-(4-methylsulfinylphenyl)-4-(4-fluorophenyl-5-(pyrid-4-yl)imidazole also having cytokine-inhibiting action. Further 2-thio-substituted imidazole derivatives are described in EP 372 445, U.S. Pat. No. 4,190,666, GB 1 155 580, JP 01-040 467, Acta Chim. 1969, 61, 69-77 and J. prakt. Chem. 1972, 314, 785-792.
It has been found that the known compounds are unstable and difficult to process, or that their efficacy is low.
In spite of the fact that numerous compounds are known, there is therefore still a need for compounds having antiinflammatory action which inhibit cytokine release.